Intramolecular β‑Alkenylation of Cyclohexanones via Pd-Catalyzed Desaturation-Mediated C(sp3)–H/Alkyne Coupling

• Published in: Journal of the American Chemical Society Vol. 142; no. 19; pp. 8962 - 8971
• Main Authors: Wang, Chengpeng, Naren, Nevin A, Zheng, Pengfei, Dong, Guangbin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.05.2020; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; FUNCTIONALIZATION; KETONES; C-H ARYLATION; PHOTOREDOX; BONDS; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; ALDEHYDES; ALKYNES; REDUCTIVE CYCLIZATION; AEROBIC DEHYDROGENATION
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c02654

Site-selective C–C bond formation through the direct coupling of C­(sp3)–H bonds with unsaturated hydrocarbons represents an atom-economical and redox-neutral way to functionalize chemically inert positions, such as those β to a carbonyl group. While most existing β-functionalization methods utilize a directing group (DG) strategy, here we report a Pd-catalyzed intramolecular β-alkenylation of ketones using alkynes as the coupling partner without the aid of DGs. Mediated by a ketone desaturation process, the reaction is redox-neutral and avoids using strong acids or bases. The resulting cis-5,6-fused bicycles can be diversely derivatized with excellent selectivity. Mechanistic studies imply an unusual “hydride-transfer” chain-like pathway, which involves the cyclometalation of an enyne intermediate and protonation of the resulting Pd enolate followed by an intermolecular hydride transfer through the desaturation of another substrate.